Effects of Resistance Exercise Among TGD Individuals Initiating Estrogen-Based Gender-Affirming Hormone Therapy (STRENGTH)

Estrogen-dominant gender-affirming hormone therapy (GAHT) is standard of care for transgender women and gender-diverse individuals and typically consists of estrogen together with anti-androgen/ testosterone therapy. Estrogen and testosterone balance influences fat and muscle mass, muscular strength and the development of sarcopenia. Sarcopenia, a condition characterized by the loss of muscular mass, strength, and function, in turn, is associated with increased mortality and adverse health outcomes. Estrogen-dominant GAHT may have deleterious effects on body composition and muscular performance that place TGD individuals at-risk for sarcopenia. As part of NCT04128488, our investigative team found that appendicular lean mass (ALM)/ height2 decreases after estrogen-based GAHT, thereby portending a higher risk for sarcopenia after GAHT. Early recognition of the changes in body composition and muscular performance leading to sarcopenia are critical, providing potential avenues to intervene and abrogate untoward downstream health effects. A promising intervention is resistance exercise, which has been shown in select populations to improve muscular mass and strength and reduce fat mass, and, thus, mitigate progression to sarcopenia in at-risk populations. For this prospective, pilot clinical trial, investigators will enroll participants who are about to be initiated on estrogen-dominant gender-affirming hormone therapy. Investigators will be randomizing participants 1:1 to either an at-home resistance exercise intervention or no exercise intervention (nutritional and exercise counseling only) for 12 weeks and assess muscle mass, strength, and function both before and after this 12-week period. The exercise intervention group will be provided with the necessary materials to complete the exercise program along with weekly virtual visits with our study team in order to learn their assigned exercises for the week. Further, survey tools will be administered to ascertain whether the resistance exercise intervention may affect gender congruence.

Study Overview

• Status: Recruiting
• Conditions: Muscle Mass and Strength
• Intervention / Treatment: Behavioral: Resistance Exercise Program; Behavioral: Nutrition and Exercise Counseling

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mabel Toribio, MD; Phone Number: 617-724-2826; Email: mptoribio@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Mabel Toribio, MD; Phone Number: 617-724-2826; Email: mptoribio@mgh.harvard.edu
      • Contact: Email: mptoribio@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years
• Initiating GAHT with estradiol (oral, sublingual, patch, injection) AND androgen suppression (leuprolide, spironolactone or bicalutamide)
• Identifies as either a transgender female/woman, gender-diverse, non-binary, gender non-confirming, gender-fluid, and/or gender-queer
• Assigned male sex at birth

Exclusion Criteria:

• Current condition(s) which may preclude the ability to participate in a resistance exercise program (including but not limited to conditions which may significantly impair mobility and balance)
• Current condition(s) where resistance exercise program may be contraindicated (including but not limited to decompensated heart failure, unstable ischemic heart disease, pulmonary hypertension, aortic aneurysm, moderate to severe valvopathies, and/or moderate to severe chronic respiratory insufficiency)
• Use of testosterone therapy for > 1 month in the last 6 months
• Use of gender-affirming hormone therapy with androgen/testosterone suppression and/or estradiol therapy within 1 year of enrollment
• Use of gender-affirming hormone therapy with androgen/testosterone suppression and/or estradiol therapy for > 1 year at any time period prior to enrollment
• History of an orchiectomy
• Current resistance exercise (including but not limited to use of resistance bands, suspension equipment, body weight exercise, free weight exercise) of 60 minutes or greater per week
• Enrollment in another study that the study investigators deem as potentially interfering with study participants or study endpoints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Resistance Exercise Intervention; Participants in this arm will be randomized to a 12-week at-home resistance exercise program.	Behavioral: Resistance Exercise Program; Participants will initiate this program at the time that they start their gender-affirming hormone therapy and will be instructed to complete resistance exercises for three 60-minute sessions per week for 12 weeks. Participants will have a weekly video call to demonstrate the exercises for that week, have a supervised training session to ensure exercises are performed safely and as instructed, monitor their continued participation in the exercise intervention, and answer any questions or issues that arise as part of the program. Further, participants will be provided with resistance bands, a TRX suspension trainer, and dumbbell weights in order to complete the resistance exercises for the program. Examples of how each exercise can be modified depending on a participant's limitations will also be provided as needed. The study team will ascertain whether they can progress to the next week's exercises depending on their ability to achieve the number of repetition's of the prior week.; Behavioral: Nutrition and Exercise Counseling; Participants will undergo lifestyle counseling related to optimization of their nutrition and exercise regimen.
Placebo Comparator: No exercise intervention; Participants in this arm will receive educational counseling on nutrition and exercising.	Behavioral: Nutrition and Exercise Counseling; Participants will undergo lifestyle counseling related to optimization of their nutrition and exercise regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appendicular lean mass/height^2	Change in appendicular lean mass/height^2 (kg/m^2) assessed via whole body DEXA in resistance exercise group	12 weeks
Gender congruence	Change in gender congruence (utilizing the total scale score from Transgender Congruence Scale) in resistance exercise group	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visceral adipose tissue mass	Change in total visceral adipose tissue mass (g) assessed using whole body DEXA in resistance exercise group	12 weeks
Visceral adipose tissue volume	Change it total visceral adipose tissue volume (cm3) assessed using whole body DEXA in resistance exercise group	12 weeks
Total fat mass	Change in total fat mass (kg) assessed using whole body DEXA in resistance exercise group	12 weeks
Total lean body mass	Change in total lean body mass (kg) assessed using whole body DEXA in resistance exercise group	12 weeks
Muscular function	Change in muscular function assessed via the 5 X sit to stand test (sec) in resistance exercise group	12 weeks
Hand-grip strength	Change in hand-grip strength (kg) assessed using a Lafayette Hand Grip Dynamometer in resistance exercise group	12 weeks
Horizontal shoulder adduction strength	Change in horizontal shoulder adduction strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group	12 weeks
Shoulder extension strength	Change in shoulder extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group	12 weeks
Elbow flexion strength	Change in elbow flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group	12 weeks
Elbow extension strength	Change in elbow extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group	12 weeks
Knee extension strength	Change in knee extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group	12 weeks
Knee flexion strength	Change in knee flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group	12 weeks
Hip extension strength	Change in hip extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group	12 weeks
Resting energy expenditure	Change in resting energy expenditure (kcal/day) assessed using a metabolic cart in the resistance exercise group	12 weeks
Resting metabolic rate	Change in resting metabolic rate (kcal/day) assessed using a metabolic cart in resistance exercise group	12 weeks
Respiratory quotient	Change in respiratory quotient (ratio) assessed using a metabolic cart in the resistance exercise group	12 weeks
Between-group change in appendicular lean body mass/ height^2	Between-group change in appendicular lean body mass/ height^2 (kg/m^2) assessed via whole body DEXA	12 weeks
Between-group change in total visceral adipose tissue mass	Between-group change in total visceral adipose tissue mass (g) assessed using whole body DEXA	12 weeks
Between-group change in visceral adipose tissue volume	Between-change in total visceral adipose tissue volume (cm3) assessed using whole body DEXA	12 weeks
Between-group change in total fat mass	Between-change in total fat mass (kg) assessed using whole body DEXA	12 weeks
Between-group change in total lean body mass	Between-group change in total lean body mass (kg) assessed using whole body DEXA	12 weeks
Between-group change in muscular function via the 5x sit to stand test	Between-group change in muscular function assessed via the 5 X sit to stand test (sec)	12 weeks
Between-group change in hand-grip strength	Between-group change in hand-grip strength (kg) assessed using a Lafayette Hand Grip Dynamometer	12 weeks
Between-group change in horizontal shoulder adduction strength	Between-group change in horizontal shoulder adduction strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer	12 weeks
Bwtween-group change in shoulder extension strength	Between-group change in shoulder extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer	12 weeks
Between-group change in elbow flexion strength	Between-group change in elbow flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer	12 weeks
Between-group change in elbow extension strength	Between-group change in elbow extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer	12 weeks
Between-group change in knee extension strength	Between-group change in knee extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer	12 weeks
Between-group change in knee flexion strength	Between-group change in knee flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer	12 weeks
Between-group change in hip extension strength	Between-group change in hip extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer	12 weeks
Between-group change in resting energy expenditure	Between-group change in resting energy expenditure (kcal/day) assessed using a metabolic cart	12 weeks
Between-group change in resting metabolic rate	Between-group change in resting metabolic rate (kcal/day) assessed using a metabolic cart	12 weeks
Between-group change in respiratory quotient	Between-group change in respiratory quotient (ratio) assessed using a metabolic cart	12 weeks
Appearance congruence	Change in appearance congruence (utilizing the appearance congruence subscale score from Transgender Congruence Scale) in resistance exercise group	12 weeks
Gender identity acceptance	Change in gender identity acceptance (utilizing the gender identity acceptance subscale score from Transgender Congruence Scale) in resistance exercise group	12 weeks
Between-group change in appearance congruence	Between-group change in appearance congruence (utilizing the appearance congruence subscale score from Transgender Congruence Scale)	12 weeks
Between-group change in gender identity acceptance	Between-group change in gender identity acceptance (utilizing the gender identity acceptance subscale score from Transgender Congruence Scale)	12 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 16, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: February 6, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Transgender women; Sarcopenia; Gender-Diverse; Estrogen-dominant gender-affirming hormone therapy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sarcopenia; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Population Characteristics; Health Status; Demography; Nutritional Status
• Other Study ID Numbers: 2025P003023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No